Project Summary/Abstract: The goal of this proposal is to launch an innovative, multi-modal neuroimaging program that will investigate the longitudinal trajectory of the neurodevelopment of irritability across the preschool period. Irritability exists on a dimension in every member of the population, however, it is also a significant mental health concern that is present in nearly every form of psychopathology and spans the internalizing/externalizing gap. Differentiating clinically salient irritability from developmentally-normative temperamental variation has proven to be a difficult task. This is made even more challenging during the preschool period, when irritability has hit its normative peak and measuring neurodevelopment is impeded by methodological constraints. This state-of-the-art program of research will 1) identify specific biomarkers underlying preschool vulnerability for psychopathology by examining neural maturation in executive function as a predictor for clinical outcome and 2) examine how the parenting environment moderates this vulnerability, with the overarching objective of identifying aberrant from normative irritable trajectories as the foundation for future brain-based behavioral intervention. Our transdisciplinary research team will recruit a sample of 150 4 year-old children, enriched for high irritability to participate in a longitudinal project. At age 4, and again at age 5, the neural underpinnings of executive function will be assessed using functional near-infrared spectroscopy (fNIRS), an optical imaging technique that is painless, non-restrictive, and reliably employed in neuroimaging studies of the prefrontal cortex in preschool children. At the transition to school-age (age 6), where a 50% rate of psychopathological symptoms have been reported in irritable children, a third fNIRS assessment will occur along with simultaneous functional magnetic resonance imaging (fMRI) to probe frontal-cortical connectivity. Well- validated and child-friendly experimental paradigms will be employed. At age 4, we will also introduce dual- person fNIRS imaging to a standardized developmentally-based laboratory interaction task in order to investigate parent-child neural synchrony, a measure of the correlation between signals of brain activity of interacting individuals. Primary analyses will 1) probe the slope of increase in prefrontal activation underlying executive function as a predictor of clinical outcome and 2) examine parent-child neural synchrony as a predictor of executive function maturation and as a moderator of clinical outcome in highly irritable children. An ambitious program of longitudinal, multi-modal neuroimaging, combined with innovative and developmentally-sensitive behavioral data collection, has the potential to identify patterns of disruption in neural processes underlying executive function so that targeted therapeutic interventions, aimed at both the child individually, and the child and parent in an interactive context, can be developed to reestablish a normative developmental trajectory.